The optic nerve is a bundle of over a million nerve fibers that connect the retina to the brain. These nerve fibers are formed by the axons of retinal ganglion cells that extend from the retina where they detect light, to the brain where they transmit visual information. Glaucoma is a class of ocular diseases resulting from damage to the optic nerve. According to the National Eye Institute, among the United States population 40 years and older there are over 2.2 million glaucoma patients (290,000 between ages 40-49). Owing to the rapid aging of the United States population, this number may increase to more than 3 million by 2020.
Glaucoma occurs when the retinal ganglion cells disposed in the optic nerve degenerate in a characteristic and identifiable pattern, called glaucomatous optic neuropathy (GON). Untreated glaucoma may lead to permanent damage of the optic nerve resulting in vision loss, which can progress to blindness. Once vision has been lost due to glaucoma, it can never be restored.
It is known that damage to the optic nerve fibers of the Retinal Nerve Fiber Layer (RNFL) often begins years before the detectable loss of visual sensitivity as measured with visual fields. However, early, microscopic damage to the optic nerve fibers is difficult to detect in vivo. Damage to the RNFL is usually only readily detectable after vision loss has already occurred. Early detection of this damage prior to vision loss would permit early medical intervention to prevent blindness.
Increased intraocular pressure (IOP) is known to be a leading cause of GON. However, there is no set threshold of intraocular pressure that causes glaucoma. Detection of glaucoma through direct measurement of intraocular pressure is therefore not reliable. One person may develop significant nerve damage at a comparatively low intraocular pressure, while another person may have a comparatively high intraocular pressure for years and never develop nerve damage.
Current screening for glaucoma is usually performed as part of a standard eye examination. The standard eye examination for detecting glaucoma includes measuring the intraocular pressure using tonometry. However, as explained above, measuring the IOP alone is an inaccurate indicator of early onset glaucoma. Other eye exams that measure changes in size or shape of the eye, anterior chamber angle, or include visible examination of the optic nerve using a slit-lamp microscope, also lack the precision to determine microcellular damage to the RNFL. A formal visual field test is also usually performed as part of a standard eye exam to ascertain if any loss of visual sensitivity has occurred. But none of these techniques can accurately detect early microscopic signs of RNFL damage.
Optical coherence tomography (OCT) has been utilized to detect microscopic damage to the RNFL. OCT can perform micron-resolution, cross-sectional imaging of biological tissue, such as the retina. In particular, OCT uses optical interferometry to amplify light reflected from a particular depth within a partially reflective sample, in this case a retina, with a resolution governed by the coherence length of the source. Light reflected from different distances may be minimized by a number of noise reduction techniques.
Current OCT methods use a single band of light, typically centered around a wavelength of 830 nm, to discriminate the RNFL from underlying tissue based on reflectance intensity alone. Because of its cellular composition, the reflectance of RNFL is usually greater at this wavelength than the surrounding retinal tissue. This marked difference in reflectance intensity facilitates segmentation of the different layers of the retina by means of an OCT scan. In advanced glaucomatous disease, the RNFL decreases in thickness due to optic neuropathy and becomes difficult to visually discern from the surrounding tissue. This makes segmentation difficult and imprecise. In addition, normal thickness varies greatly within the RNFL, so typically a large decrease in thickness must occur before it is noticeably statistically different from normal.
The retina is comprised of several cellular layers that each have distinct reflective properties. For example, disposed between the retinal pigment epithelium and the inner limiting membrane (ILM) is the RNFL, the inner plexiform layer (IPL), and the inner nuclear layer (INL). Because of the complexity and number of retinal structures, segmenting the retinal layers may be necessary to accurately measure the reflectance from the RNFL. Such segmentation of the RNFL may be difficult due to the varying of thickness within the RNFL.
The RNFL is comprised of cylindrical fibers, making the reflectance from OCT directionally dependent. This can cause variable intensity contrast between tissue layers and thus additional difficulties in segmentation. This also causes reduced signal strength in nasal retina. Because segmentation is based solely on intensity, differences in the RNFL become difficult to discern when the RNFL becomes thin Segmentation algorithms will frequently follow retinal tissue boundaries to produce a layer identified as RNFL. However, these algorithms break down and become inaccurate when applied to retinas having damaged RNFLs. Often other retinal tissues are included in the RNFL layer as determined by the segmentation algorithms. This leads to inaccuracies and makes identifying damaged tissue unreliable.
It is therefore desirable to provide a method of accurately segmenting retinal tissues and determining the boundaries between the RNFL and surrounding tissue.
It is also desirable to provide a method for detecting early changes in the RNFL before visual sensitivity is lost, allowing early treatment to save axons.
It is also desirable to provide an OCT method that relies on spectral characteristics of the RNFL that are less sensitive to the direction of illumination and will provide a more accurate measure of the RNFL in clinical practice.